Characterization of extensive 2-fluorodeschloroketamine metabolism in pooled human liver microsomes, urine and hair from an addicted patient using high-resolution accurate mass spectrometry - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Analytical Toxicology Année : 2023

Characterization of extensive 2-fluorodeschloroketamine metabolism in pooled human liver microsomes, urine and hair from an addicted patient using high-resolution accurate mass spectrometry

Résumé

2-Fluorodeschloroketamine (2F-DCK) is a ketamine derivative involved in acute intoxications and deaths. The aim of this study is to investigate its metabolism using pooled human liver microsomes (pHLMs) and to apply it to authentic samples (urine, hair and seized materials) from a drug user. 2F-DCK (100 µM) incubates with pHLMs were analyzed by liquid chromatography-high-resolution accurate mass (LC-HRAM; Q-Exactive, Thermo Fisher Scientific®) according to a previously published protocol. Spectra annotation was performed using Compound Discoverer® software and the metabolic scheme was drawn using ChemDraw software. Urine (200 µL) and hair (previously decontaminated using dichloromethane and segmented into three segments: A, 0-3 cm; B, 3-6 cm; C, 6-9 cm) were extracted with a mixture of hexane:ethyl acetate (1:1) and chloroform:isopropanol (4:1). About 10 µL of both reconstituted residues were analyzed by LC-HRAM. Hair was also analyzed by LC-MS-MS (TSQ Vantage, Thermo Fisher Scientific®) for 2F-DCK and deschloroketamine (DCK) quantification. The two presumed 2F-DCK crystals consumed by the patient were dissolved in methanol (1 mg/mL) and 10 µL were analyzed by LC-MS-MS (Quantum Access Max, Thermo Fisher Scientific®). Twenty-six putative 2F-DCK metabolites were identified, 15 being reported for the first time. Thirteen metabolites were detected in pHLMs, 10 confirmed in both the patient's urine and hair and all were found in at least one of the two samples. Twenty-three metabolites were detected in urine and 20 in hair. Our research confirms the reliability of nor-2F-DCK as a target analyte and suggests OH-dihydro-nor-2F-DCK and dehydro-nor-2F-DCK as new target analytes in urine and hair, respectively. This is the first study to report DCK as a 2F-DCK metabolite using pHLMs and to determine its concentrations in hair (A/B/C, 885/1,500/1,850 pg/mg) following chronic use. Finally, the two seized crystals contained 2F-DCK at 67% and 96% with traces of DCK (0.4% and 0.6%) related to cross-contamination by container exchange.

Domaines

Toxicologie
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Dates et versions

hal-04191609 , version 1 (30-08-2023)

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Delphine Joseph, Camille Lesueur, Fanny Zerizer, Alexia Fenot, Jean Claude Alvarez, et al.. Characterization of extensive 2-fluorodeschloroketamine metabolism in pooled human liver microsomes, urine and hair from an addicted patient using high-resolution accurate mass spectrometry. Journal of Analytical Toxicology, 2023, 47 (6), pp.504-516. ⟨10.1093/jat/bkad030⟩. ⟨hal-04191609⟩
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